The Journal of Pathology: Clinical Research (May 2023)
p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
- Martin Köbel,
- Eun‐Young Kang,
- Ashley Weir,
- Peter F Rambau,
- Cheng‐Han Lee,
- Gregg S Nelson,
- Prafull Ghatage,
- Nicola S Meagher,
- Marjorie J Riggan,
- Jennifer Alsop,
- Michael S Anglesio,
- Matthias W Beckmann,
- Christiani Bisinotto,
- Michelle Boisen,
- Jessica Boros,
- Alison H Brand,
- Angela Brooks‐Wilson,
- Michael E Carney,
- Penny Coulson,
- Madeleine Courtney‐Brooks,
- Kara L Cushing‐Haugen,
- Cezary Cybulski,
- Suha Deen,
- Mona A El‐Bahrawy,
- Esther Elishaev,
- Ramona Erber,
- Sian Fereday,
- AOCS Group,
- Anna Fischer,
- Simon A Gayther,
- Arantzazu Barquin‐Garcia,
- Aleksandra Gentry‐Maharaj,
- C Blake Gilks,
- Helena Gronwald,
- Marcel Grube,
- Paul R Harnett,
- Holly R Harris,
- Andreas D Hartkopf,
- Arndt Hartmann,
- Alexander Hein,
- Joy Hendley,
- Brenda Y Hernandez,
- Yajue Huang,
- Anna Jakubowska,
- Mercedes Jimenez‐Linan,
- Michael E Jones,
- Catherine J Kennedy,
- Tomasz Kluz,
- Jennifer M Koziak,
- Jaime Lesnock,
- Jenny Lester,
- Jan Lubiński,
- Teri A Longacre,
- Maria Lycke,
- Constantina Mateoiu,
- Bryan M McCauley,
- Valerie McGuire,
- Britta Ney,
- Alexander Olawaiye,
- Sandra Orsulic,
- Ana Osorio,
- Luis Paz‐Ares,
- Teresa Ramón y Cajal,
- Joseph H Rothstein,
- Matthias Ruebner,
- Minouk J Schoemaker,
- Mitul Shah,
- Raghwa Sharma,
- Mark E Sherman,
- Yurii B Shvetsov,
- Naveena Singh,
- Helen Steed,
- Sarah J Storr,
- Aline Talhouk,
- Nadia Traficante,
- Chen Wang,
- Alice S Whittemore,
- Martin Widschwendter,
- Lynne R Wilkens,
- Stacey J Winham,
- Javier Benitez,
- Andrew Berchuck,
- David D Bowtell,
- Francisco J Candido dos Reis,
- Ian Campbell,
- Linda S Cook,
- Anna DeFazio,
- Jennifer A Doherty,
- Peter A Fasching,
- Renée T Fortner,
- María J García,
- Marc T Goodman,
- Ellen L Goode,
- Jacek Gronwald,
- David G Huntsman,
- Beth Y Karlan,
- Linda E Kelemen,
- Stefan Kommoss,
- Nhu D Le,
- Stewart G Martin,
- Usha Menon,
- Francesmary Modugno,
- Paul DP Pharoah,
- Joellen M Schildkraut,
- Weiva Sieh,
- Annette Staebler,
- Karin Sundfeldt,
- Anthony J Swerdlow,
- Susan J Ramus,
- James D Brenton
Affiliations
- Martin Köbel
- Department of Pathology and Laboratory Medicine University of Calgary, Foothills Medical Center Calgary AB Canada
- Eun‐Young Kang
- Department of Pathology and Laboratory Medicine University of Calgary, Foothills Medical Center Calgary AB Canada
- Ashley Weir
- School of Clinical Medicine UNSW Medicine and Health, University of NSW Sydney Sydney New South Wales Australia
- Peter F Rambau
- Department of Pathology and Laboratory Medicine University of Calgary, Foothills Medical Center Calgary AB Canada
- Cheng‐Han Lee
- Department of Pathology and Laboratory Medicine University of Alberta Edmonton AB Canada
- Gregg S Nelson
- Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine University of Calgary Calgary AB Canada
- Prafull Ghatage
- Department of Oncology, Division of Gynecologic Oncology, Cumming School of Medicine University of Calgary Calgary AB Canada
- Nicola S Meagher
- School of Clinical Medicine UNSW Medicine and Health, University of NSW Sydney Sydney New South Wales Australia
- Marjorie J Riggan
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Duke University Medical Center Durham NC USA
- Jennifer Alsop
- Centre for Cancer Genetic Epidemiology, Department of Oncology University of Cambridge Cambridge UK
- Michael S Anglesio
- Department of Obstetrics and Gynecology University of British Columbia Vancouver BC Canada
- Matthias W Beckmann
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen‐EMN Friedrich‐Alexander University Erlangen‐Nuremberg, University Hospital Erlangen Erlangen Germany
- Christiani Bisinotto
- Department of Gynecology and Obstetrics, Ribeirão Preto Medical School University of São Paulo Ribeirão Preto Brazil
- Michelle Boisen
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh PA USA
- Jessica Boros
- Centre for Cancer Research The Westmead Institute for Medical Research, University of Sydney Sydney New South Wales Australia
- Alison H Brand
- Department of Gynaecological Oncology Westmead Hospital Sydney New South Wales Australia
- Angela Brooks‐Wilson
- Canada's Michael Smith Genome Sciences Centre, BC Cancer Vancouver BC Canada
- Michael E Carney
- Department of Obstetrics and Gynecology, John A. Burns School of Medicine University of Hawaii Honolulu HI USA
- Penny Coulson
- Division of Genetics and Epidemiology The Institute of Cancer Research London UK
- Madeleine Courtney‐Brooks
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh PA USA
- Kara L Cushing‐Haugen
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center Seattle WA USA
- Cezary Cybulski
- Department of Genetics and Pathology, International Hereditary Cancer Center Pomeranian Medical University Szczecin Poland
- Suha Deen
- Department of Histopathology Nottingham University Hospitals NHS Trust, Queen's Medical Centre Nottingham UK
- Mona A El‐Bahrawy
- Department of Metabolism, Digestion and Reproduction Imperial College London, Hammersmith Hospital London UK
- Esther Elishaev
- Department of Pathology University of Pittsburgh School of Medicine Pittsburgh PA USA
- Ramona Erber
- Institute of Pathology, Comprehensive Cancer Center Erlangen‐EMN, Friedrich‐Alexander University Erlangen‐Nuremberg, University Hospital Erlangen Erlangen Germany
- Sian Fereday
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
- AOCS Group
- Centre for Cancer Research The Westmead Institute for Medical Research, University of Sydney Sydney New South Wales Australia
- Anna Fischer
- Institute of Pathology and Neuropathology, Tuebingen University Hospital Tuebingen Germany
- Simon A Gayther
- Center for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars‐Sinai Medical Center Los Angeles CA USA
- Arantzazu Barquin‐Garcia
- HM Sanchinarro Centro Integral Oncológico Clara Campal University Hospital Madrid Spain
- Aleksandra Gentry‐Maharaj
- MRC Clinical Trials Unit Institute of Clinical Trials & Methodology, University College London London UK
- C Blake Gilks
- Department of Pathology and Laboratory Medicine University of British Columbia Vancouver BC Canada
- Helena Gronwald
- Department of Propaedeutics, Physical Diagnostics and Dental Physiotherapy Pomeranian Medical University Szczecin Poland
- Marcel Grube
- Department of Women's Health Tuebingen University Hospital Tuebingen Germany
- Paul R Harnett
- Discipline of Obstetrics and Gynaecology The University of Sydney Sydney New South Wales Australia
- Holly R Harris
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center Seattle WA USA
- Andreas D Hartkopf
- Department of Women's Health Tuebingen University Hospital Tuebingen Germany
- Arndt Hartmann
- Institute of Pathology, Comprehensive Cancer Center Erlangen‐EMN, Friedrich‐Alexander University Erlangen‐Nuremberg, University Hospital Erlangen Erlangen Germany
- Alexander Hein
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen‐EMN Friedrich‐Alexander University Erlangen‐Nuremberg, University Hospital Erlangen Erlangen Germany
- Joy Hendley
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
- Brenda Y Hernandez
- Cancer Epidemiology Program University of Hawaii Cancer Center Honolulu HI USA
- Yajue Huang
- Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester MN USA
- Anna Jakubowska
- Department of Genetics and Pathology, International Hereditary Cancer Center Pomeranian Medical University Szczecin Poland
- Mercedes Jimenez‐Linan
- Department of Histopathology Addenbrooke's Hospital Cambridge UK
- Michael E Jones
- Division of Genetics and Epidemiology The Institute of Cancer Research London UK
- Catherine J Kennedy
- Centre for Cancer Research The Westmead Institute for Medical Research, University of Sydney Sydney New South Wales Australia
- Tomasz Kluz
- Department of Gynecology and Obstetrics Institute of Medical Sciences, Medical College of Rzeszow University Rzeszów Poland
- Jennifer M Koziak
- Alberta Health Services‐Cancer Care Calgary AB Canada
- Jaime Lesnock
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh PA USA
- Jenny Lester
- David Geffen School of Medicine, Department of Obstetrics and Gynecology University of California at Los Angeles Los Angeles CA USA
- Jan Lubiński
- Department of Genetics and Pathology, International Hereditary Cancer Center Pomeranian Medical University Szczecin Poland
- Teri A Longacre
- Department of Pathology Stanford University School of Medicine Stanford CA USA
- Maria Lycke
- Department of Obstetrics and Gynecology Institute of Clinical Science, Sahlgrenska University Hospital, University of Gothenburg Gothenburg Sweden
- Constantina Mateoiu
- Department of Pathology University of Gothenburg Gothenburg Sweden
- Bryan M McCauley
- Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic Rochester MN USA
- Valerie McGuire
- Department of Epidemiology and Population Health Stanford University School of Medicine Stanford CA USA
- Britta Ney
- Institute of Pathology and Neuropathology, Tuebingen University Hospital Tuebingen Germany
- Alexander Olawaiye
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh PA USA
- Sandra Orsulic
- David Geffen School of Medicine, Department of Obstetrics and Gynecology University of California at Los Angeles Los Angeles CA USA
- Ana Osorio
- Genetics Service, Fundación Jiménez Díaz Madrid Spain
- Luis Paz‐Ares
- H12O‐CNIO Lung Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO) Madrid Spain
- Teresa Ramón y Cajal
- Medical Oncology Service Hospital Sant Pau Barcelona Spain
- Joseph H Rothstein
- Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA
- Matthias Ruebner
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen‐EMN Friedrich‐Alexander University Erlangen‐Nuremberg, University Hospital Erlangen Erlangen Germany
- Minouk J Schoemaker
- Division of Genetics and Epidemiology The Institute of Cancer Research London UK
- Mitul Shah
- Centre for Cancer Genetic Epidemiology, Department of Oncology University of Cambridge Cambridge UK
- Raghwa Sharma
- Tissue Pathology and Diagnostic Oncology Westmead Hospital Sydney New South Wales Australia
- Mark E Sherman
- Department of Health Sciences Research, Mayo Clinic Jacksonville FL USA
- Yurii B Shvetsov
- Cancer Epidemiology Program University of Hawaii Cancer Center Honolulu HI USA
- Naveena Singh
- Department of Pathology and Laboratory Medicine University of British Columbia Vancouver BC Canada
- Helen Steed
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology University of Alberta Edmonton AB Canada
- Sarah J Storr
- Nottingham Breast Cancer Research Centre Biodiscovery Institute, University of Nottingham Nottingham UK
- Aline Talhouk
- Department of Obstetrics and Gynecology University of British Columbia Vancouver BC Canada
- Nadia Traficante
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
- Chen Wang
- Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic Rochester MN USA
- Alice S Whittemore
- Department of Epidemiology and Population Health Stanford University School of Medicine Stanford CA USA
- Martin Widschwendter
- EUTOPS Institute, University of Innsbruck Innsbruck Austria
- Lynne R Wilkens
- Cancer Epidemiology Program University of Hawaii Cancer Center Honolulu HI USA
- Stacey J Winham
- Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic Rochester MN USA
- Javier Benitez
- Centre for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III Madrid Spain
- Andrew Berchuck
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology Duke University Medical Center Durham NC USA
- David D Bowtell
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
- Francisco J Candido dos Reis
- Department of Gynecology and Obstetrics, Ribeirão Preto Medical School University of São Paulo Ribeirão Preto Brazil
- Ian Campbell
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
- Linda S Cook
- Epidemiology, School of Public Health University of Colorado Aurora CO USA
- Anna DeFazio
- The Daffodil Centre The University of Sydney, a Joint Venture with Cancer Council NSW Sydney New South Wales Australia
- Jennifer A Doherty
- Huntsman Cancer Institute, Department of Population Health Sciences University of Utah Salt Lake City UT USA
- Peter A Fasching
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen‐EMN Friedrich‐Alexander University Erlangen‐Nuremberg, University Hospital Erlangen Erlangen Germany
- Renée T Fortner
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg Germany
- María J García
- Computational Oncology Group, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO) Madrid Spain
- Marc T Goodman
- Cancer Prevention and Control Program, Cedars‐Sinai Cancer, Cedars‐Sinai Medical Center Los Angeles CA USA
- Ellen L Goode
- Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic Rochester MN USA
- Jacek Gronwald
- Department of Genetics and Pathology, International Hereditary Cancer Center Pomeranian Medical University Szczecin Poland
- David G Huntsman
- Department of Obstetrics and Gynecology University of British Columbia Vancouver BC Canada
- Beth Y Karlan
- David Geffen School of Medicine, Department of Obstetrics and Gynecology University of California at Los Angeles Los Angeles CA USA
- Linda E Kelemen
- Division of Acute Disease Epidemiology, South Carolina Department of Health & Environmental Control Columbia SC USA
- Stefan Kommoss
- Department of Women's Health Tuebingen University Hospital Tuebingen Germany
- Nhu D Le
- Cancer Control Research, BC Cancer Agency Vancouver BC Canada
- Stewart G Martin
- Nottingham Breast Cancer Research Centre Biodiscovery Institute, University of Nottingham Nottingham UK
- Usha Menon
- MRC Clinical Trials Unit Institute of Clinical Trials & Methodology, University College London London UK
- Francesmary Modugno
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh School of Medicine Pittsburgh PA USA
- Paul DP Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Oncology University of Cambridge Cambridge UK
- Joellen M Schildkraut
- Department of Epidemiology, Rollins School of Public Health Emory University Atlanta GA USA
- Weiva Sieh
- Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA
- Annette Staebler
- Institute of Pathology and Neuropathology, Tuebingen University Hospital Tuebingen Germany
- Karin Sundfeldt
- Department of Obstetrics and Gynecology, Institute of Clinical Science Sahlgrenska Center for Cancer Research, University of Gothenburg Gothenburg Sweden
- Anthony J Swerdlow
- Division of Genetics and Epidemiology The Institute of Cancer Research London UK
- Susan J Ramus
- School of Clinical Medicine UNSW Medicine and Health, University of NSW Sydney Sydney New South Wales Australia
- James D Brenton
- Cancer Research UK Cambridge Institute, University of Cambridge Cambridge UK
- DOI
- https://doi.org/10.1002/cjp2.311
- Journal volume & issue
-
Vol. 9,
no. 3
pp. 208 – 222
Abstract
Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
Keywords
